10-aminoalkyl-9,10-dihydroanthracenes

ABSTRACT

10-Aminoalkyl-9,10-dihydroanthracenes wherein the nucleus is substituted by halogen, lower alkyl, trifluoromethyl, lower alkylthio, lower alkylsulfonyl or N,N-dimethyl-sulfamyl and the amino group may be mono or dialkyl substituted as well as a monocyclic heterocyclic amino moiety are tranquilizers. Corresponding 9-lower alkyl or 9-phenyl derivatives also have utility as antidepressants. Compounds are generally prepared by reaction of a 10-bromoalkyl-anthracene with an appropriate amine followed by reduction to the 9,10-dihydroanthracene. 9-Substituted-10-aminoalkyl-9,10-dihydroanthracenes which are not benzo ring substituted have antidepressant activity with no tranquilizing activity. These compounds are generally prepared by alkylation of the 9,10-dihydroanthracene with an aminoalkyl halide.

United States Patent [72] Inventors Paul N. Craig Ambler; Charles L.Zirkle, Berwyn, both of Pa.

[2!] Appl. No. 742,171

[22] Filed July 3, 1968 [45] Patented Nov. 23, 1971 [73] Assignee Smith,Kline 8: French Laboratories Philadelphia, Pa. Continuation-impart ofapplication Ser. No. 631,584, Apr. 18, 1967, now abandonedContinuation-impart of application Ser. No. 526,975, Feb. 14, 1966, nowabandoned. This application July 3, 1968, Ser. No. 742,171

[54] 10-AMlNOALKYL-9,IO-DIHYDROANTHRACENES 24 Claims, No Drawings [51]Int. Cl C07d 87/28 [50] Field of Search 260/570.8

TC,501.l,501.l2, 343.7,253,570.8, 501.1. 50l.l2,32l,253

[56] References Cited UNITED STATES PATENTS 7/ l 946 Cusic OTHERREFERENCES Davis et a1. .lour. Med. Chem," Vol. 7, pages 88- 90 (1964)Mjchajlyszyn et al., Coll. Czech. Chem. Comm.," Vol. 24, pages 3955-3956 1957) Primary Examiner-Robert V. Hines Attorneys-William H.Edgerton, Richard D. Foggio, Joan S. Keps, Arthur R. Eglington, Aland D.Lourie and Joseph A. Marlino ABSTRACT: l0-Aminoalkyl-9, lO-dihydroanthracenes wherein the nucleus is substituted by halogen,lower alkyl, trifluoromethyl, lower alkylthio, lower alkylsulfonyl orN,N- dimethyl-sulfamyl and the amino group may be mono or dialkylsubstituted as well as a monocyclic heterocyclic amino moiety aretranquilizers. Corresponding 9-l0wer alkyl or 9- phenyl derivatives alsohave utility as antidepressants. Compounds are generally prepared byreaction of a IO-bromoalkyl-anthracene with an appropriate aminefollowed by reduction to the 9, l O-dihydroanthracene.

9-Substituted- I 0-aminoalkyl-9, I O-dihydroanthracenes which are notbenzo ring substituted have antidepressant activity with notranquilizing activity. These compounds are generally prepared byalkylation of the 9,l0dihydroanthracene with an aminoalkyl halide.

lO-AMINOALKYL-9, IO-DIHYDROANTHRACENES This application is acontinuation-in-part of application Ser. No. 631,584 filed Apr. l8, i967and now abandoned which is a continuation-in-part of application Ser.No. 526,975 filed Feb. 14, 1966 and now abandoned.

This invention relates to novel substituted IO-aminoalkyl-9,10-dihydroanthracenes which have useful phamiacodynamic properties.More specifically the novel products of this invention effect thecentral nervous system and have utility as tranquilizers. Thetranquilizing activity is demonstrated in standard pharmacological testprocedures employed in characterizing chlorpromazine and trifluoperazineat oral dosages in rats, mice and monkeys approximately equivalent tothe latter agents.

The novel l-aminoalkyl-9,lO-dihydroanthracenes of this invention arerepresented by the following general structural formula:

5 ICE 4 6 9 3 FORMULA i when:

R represents hydrogen, lower alkyl, such as methyl or ethyl, or phenyl;

Y represents halogen having an atomic weight of less than 80, preferablychlorine, lower alkyl such as methyl, trifluoromethyl, lower alkylthiosuch as methylthio, lower alkylsulfonyl such as methylsulfonyl orN,N-dimethyl-sulfamyl;

A represents an alkylene chain, straight or branched, of from two tofour carbon atoms, and

2 represents amino, mono-loweralkylamino, di-loweralkylamino, or amonocyclic heterocyclic amino moiety containing from four to 12 carbonatoms, and containing a maximum of two hetero ring members selected fromthe group of oxygen, nitrogen and sulfur, such as particularlymorpholinyl, thiamorpholinyl, N-pyrrolidinyl, N-piperidinyl,n-lower-alkyl- N-piperazinyl, N-(w-hydroxy-lower-alkyl)-N-piperazinyl,N'- (w-hydroxy-alkoxy-lower-alkyl)-N-piperazinyl orN'-(wacetoxy-lower-alkyl)-N-piperazinyl.

Advantageous compounds of this invention are represented by thefollowing formula:

( JHzCHCHr-Z FORMULA ll Particularly advantageous compounds are 10-(3-dimethylaminopropyl )-2-trifluoromethyl-9, l 0- dihydroanthracene and9-methyl- 10-(3- dimethylaminopropyl)-2-trifluoromethyl-9,l0-dihydroanthracene.

Compounds of formulas l and ll above wherein R is lower alkyl or phenyl,in addition to having tranquilizing activity,

also have utility as antidepressants. The antidepressant activity isdemonstrated in standard pharmacological test procedures employed incharacterizing imipramine and amitryptyline at oral dosages in mice andrats approximately equivalent to the latter agents.

By the terms lower alkyl or alkoxy where used herein alone or incombustion with other terms, groups having from one to four, preferablyone to two carbon atoms are indicated.

This invention also includes stable, pharmaceutically acceptable, acidaddition salts of the above defined bases formed with nontoxic organicand inorganic acids. Such salts are easily prepared by methods known tothe art. The base is reacted with either the calculated amount oforganic or inorganic acid in aqueous miscible, solvent such as acetoneor ethanol, with isolation of the salt by concentration and cooling oran excess of the acid in aqueous immiscible solvent, such as ethyl etheror chlorofon'n, with the desired salt separating directly. Exemplary ofsuch organic salts are those with maleic, fumaric, benzoic, ascorbic,pamoic, succinic, bismethylenesalicyclic, methane-sulfonic,ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric,gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic,stearic, palmitic, itaconic, glycolic, paminobenzoic, glutamic, benzenesulfonic and theophylline acetic acids as well as with the8chlorotheophylline and 8- bromotheophylline. Exemplary of suchinorganic salts are those with hydrochloric, hydrobromic, sulfuric,sulfamic, phosphoric, and nitric acids. These salts may also be preparedby the classical method of double decomposition of appropriate saltswhich is well known to the art.

The l0-aminoalkyl-9,lO-dihydroanthracenes of this invention are preparedby one of several routes depending on the nuclear (Y) substituent andthe presence of a 9-alkyl or phenyl group. When the 9-position isunsubstituted (R=H) the products are obtained advantageously via thefully aromatic anthracenes which are prepared as shown in the followingsynthetic scheme illustrated by way of example for 2 represented bydimethylamino:

(L) HO A -O CH;

HN CH) Y a 2 CHzO-A-MgX lHBr FORMULA ill in which Y AND A are as definedin Formula l and X is halogen, preferably chlorine.

According to the above procedure, the substituted anthrone is reactedwith a methoxyalkyl magnesium halide to give the lO-methoxyalkyllO-hydroxy-9, l O-dihydroanthracenes. Advantageously the reaction iscarried out in an inert organic solvent such as ether, for examplediethyl ether, dioxane or, preferably, tetrahydrofuran at a temperatureof from about 0 C. to room or ambient temperature for a period of about3 to 24 hours. Removal of the solvent and treatment of the residue withwater and/or an ammonium salt solution separates the lO-methoxyalkylderivative. The latter is treated with concentrated (48 percent)hydrobromic acid to give simultaneous dehydration of the IO-hydroxygroup and cleavage of the methyl ether linkage. The resultinglO-bromoalkylanthracenes are treated with a di-loweralkylamine as shownabove or ammonia, a mono-loweralkylamine, pyrrolidine, piperidine,N-lower alkyl-piperazine or N-( w-acetoxy-lower-alkyl)-piperazine togive the corresponding aminoalkylanthracenes of formula [11. The latteruseful intermediates are reduced to give the 9,l0-dihydroanthraceneproducts of this invention with phosphorus and hydrogen iodide or withhydrogen and copper chromite catalyst when Y is trifluoromethyl.

Hydrolysis of the Nacetoxyalkyl-N-piperazinyl products thus formed withfor example sodium hydroxide solution yields the correspondingN'-(m-hydroxy-lower-alkyl)-N- piperazinyl derivatives of Formula I.Further alkylation of the N-piperazinyl compounds thus obtained with analkylene oxide or alkylene halohydrin yields other N'-substitutedpiperazinyl compounds of formula I.

The 9-unsubstituted anthrone starting materials used as above are eitherknown or prepared conveniently as illustrated by the following outlineof the preparation of 2- trifluoromethyl-lOanthrone. Phenyl magnesiumbromide is reacted with 2bromo-4-trifluoromethylbenzonitrile to give 2-bromo-4-trifluoromethylbenzophenone. The latter is reduced with forexample phosphorus and hydrogen iodide to yield 2-bromo-4-tritluoromethyl-diphenylmethane, which is reacted first withmagnesium, then with carbon dioxide to give 2-benzyl-5trifluromethylbenzoic acid. Cyclization by acid treatment withfor example concentrated sulfuric acid furnishes the 2-trifluoromethyllO-anthrone.

The compounds of formula I when R is lower alkyl or phenyl andespecially when Y is trifluoromethyl are prepared as shown in thefollowing sequence illustrated by way of example for R is methyl and Zis dimethylamino:

According to the above procedure. the substituted2-(amethylbenzyl)-benzonitrile is reacted with a methoxyalkyl magnesiumhalide as described more fully hereinabove to give the methoxyalkylimine derivative. The latter is treated with concentrated (48 percent)hydrobromic acid to simultaneously ring close and cleave themethyl etherlinkage The resulting lO-bromoalkyl-anthracene is treated with theappropriate amine to give the corresponding lO-aminoalkylanthracenewhich is reduced with, preferably, hydrogen and copper chromite catalystto the 9-alkyl-9,l0 dihydroanthracene product.

The benzonitrile starting materials used as above are either known orprepared conveniently as illustrated by the following outline of thepreparation of 2-(a-methylbenzyl)5- trifluoromethylbenzonitrile.2-Bromo-4-trifluoromethylbenzophenone is reacted with a tri-loweralkylsulfoxonium halide such as trimethylsulfoxonium iodide in a suitableorganic solvent for example dimethyl sulfoxide is usually in thepresence of a strong alkali such as an alkali metal hydride, i.e. sodiumor potassium hydride or an alkali metal lower alkoxide such as sodiummethylate or ethylate to give l-phenyl-l-( 2-bromo-4-trifluoromethylphenyl)-ethylene oxide. The latter is reducedwith a bimetallic hydride such as lithium aluminum hydride in a suitablenonpolar organic solvent such as ethyl ether or tetrahydrofuran toa-phenyl-a-(2-bromo-4- trifluoromethylphenyl)-ethanol. This alcohol isthen reduced with phosphorus and hydrogen iodide to 2-(a-methylbenzyl)-5trifluoromethyl-bromobenzene which is treated with cuprous cyanide togive the corresponding benzonitrile. Alternatively, this benzonitrilemay be hydrolyzed to the benzoic acid and cyclized with for example9acid to give 9-methyl- 2- trifluoromethyl-lO-anthrone which may beconverted to products of this invention as described hereinabove.

Either of the two general procedures described above for the preparationof compounds of formula I may be interchanged. For example,2-bromo-4-trifluoromethyldiphenylmethane is converted with cuprouscyanide to the 2-benzyl- S-trifluoromethylbenzoitrile which is thenreacted with a methoxyalkyl magnesium halide to give the imine followedby similar reactions as described above to furnish the corresponding9-unsubstituted-9, l O-dihydrozinthracene products.

Some of the compounds of this invention may be present as cis or transisomers as well as mixtures of these isomers. For example, when R informula I is other than hydrogen the geometrical isomers may berepresented as follows:

E R R. H

H A-Z H AZ The isomers are separated by fractional crystallization oftheir acid addition salts from a suitable solvent or mixture of solventssuch as, for example, acetone-ether or ethanol-ether, Also, a pureisomer may be obtained directly from the reduction of the IO-aminoalkylanthracene.

In addition, it will be readily apparent to one skilled in the art thatcertain compounds of this invention may be present as optical isomers.These isomers are separated by recrystallization of the optically activeacid addition salts, for example the d-and l-di-p-toluoyltartrates ofthe racemic free base. Alternatively, a precursor in the synthesis ofthe products of formula I may be resolved into d-and l-isomers and theseparated isomers reacted further to give the optically active products.

The connotation of the general formulas presented herein is to includeall isomers, the separated d or 1 optical isomers as well as the a lmixture and the separated cis or trans isomers as well as the mixture ofthese isomers.

A useful pharmacological indicator of tranquilizing activity is theproduction of ptosis in rats. In this procedure rats are examined afteroral administration of a test compound at hourly intervals for a ptoticefiect and the incidence of ptosis is recorded as a percentage of thenumber of test animals. Another test procedure for evaluatingtranquilizing activity is the suppression of rage in mice. A testcompound is administered orally to mice preselected for their ability toexhibit rage episodes during footshock and the animals are tested again.The percentage of animals exhibiting protection against rage isrecorded.

Antidepressant activity is measured pharmacologically by the ability ofa compound to prevent reserpine-induced ptosis in rats or mice. In thisprocedure a test compound is administered orally to the animals followedat various time intervals by l mg./kg. of reserpine (iv) and the testanimals are observed 45 minutes thereafter for ptosis prevention.

The following table 1 sets forth comparative data obtained by employingthe above described test procedures for selected compounds of thisinvention and the closest known prior art l0-aminoalkyl-9, lO-dihydroanthracenes.

TABLE 1 Oral Rat ptosis, drse, maximum percent In g ire e Pro- Pro-Compound base) duction vention A 29 0.... m 29 B-. CH CH; 44 45.4

(CHz)a-' (CH:4)2

Austria 223,611

C 2. 7 5. 4 10. 8 21. 6 75. 0 C Fa ED50=1L1 mg./kg.

(CHr)iN( Ha)1 D Cis isomer H CH: 30 30 10 50 80 43. 4 80 C F a ED50=14.5IngJkg.

H (CF2)aN(CH:)z

From the above table it is observed that the prior art compounds A and Bare either inactive or demonstrate activity at doses considerably higherthan compounds C and D of the invention.

In general the separated !-isomer of a racemic compound of thisinvention is more active phannacologically than corresponding racemicmixture as illustrated in table 2 for tranquilizing activity.

As noted hereinabove the compounds of formulas l and ll wherein R islower alkyl or phenyl have both tranquilizing and antidepressantactivity. Thus the compound D in table 1 has an ED of 14.5 mg./kg. inthe rat ptosis prevention test (antidepressant activity) and the samecompound B (dl-isomer) in table 2 has an ED of 32.1 mg./kg. in the mousesuppression test (tranquilizing activity). To demonstrate that compoundsof formulas l and ll when R is hydrogen do not have antidepressantactivity, test results are shown in table 3 for mouse ptosis prevention.

Thus. although the parent compound A shown in table 3 has noantidepressant activity, the presence of a 9-methyl substituent incompound B incorporates a component of antidepressant activity whileretaining the already present tranquilizing activity of the parentcompound A.

A further aspect of this invention relates to9-substitutedlO-aminoalkyl-Q,lO-dihydroanthracenes which are not benzoring substituted. These compounds have antidepressant activity with notranquilizing activity. The antidepressant activity is demonstrated instandard phannacological test procedures employed in characterizingimipramine and amitryptyline at oral dosages in mice and ratsapproximately equivalent to the latter agents. These9-substituted-lO-aminoalkyl-9,l0- dihydroanthracenes are represented bythe following general structural formula:

ill: 0 H

(I l-I A Z Formula IV when.

R represents lower alkyl. such as methyl or ethyl, or phenyl; and

A and Z are as defined in formula I above.

The compounds of the formula IV are prepared ad vantageously by directalkylation of an R -substituted-9.l0- dihydroanthracene with a tertiaryaminoalkyl halide, such as dimethylaminopropyl chloride, in an inertorganic solvent. for example dimethylsulfoxide or an ether Preferably analkali metal salt of the 9,10-dihydroanthracene is employed which isprepared for example from the sodium hydride or butyl lithi um.Alternatively, methods analogous to those described for the preparationof compounds of formula I above may be employed to obtain compounds offonnula lV Similarly these compounds may be present as cis, transisomers which are separated by fractionation Also, a pure cis isomerupon treat ment with sodium hydride m dimethylsulfoxide gives a mixtureof cis, trans isomers from which the pure trans isomer IS separated.

In contrast to the compounds of formulas I and 11 wherein R is loweralkyl or phenyl which have both tranquilizing and antidepressantactivity, the compounds of formula [V which share the structural featureof 9-substituent but lack the benzo ring substituent have antidepressantactivity but no tranquilizing activity. This is shown in the followingtable 4.

The novel compounds of this invention may be administered orally orparenterally in conventional dosage unit forms such as tablets,capsules, injectables or the like, by incorporating the appropriate doseof compound of formula 1 or IV with carriers according to acceptedpharmaceutical practices. In practice, unit doses of from 10 mg. to 250mg. administered from one to four times a day are effective.

The following examples are not limiting but are illustrative ofcompounds of this invention and procedures for their preparation andwill serve to make fully apparent all of the compounds embraced by thegeneral formulas given above. Alternatives and modifications of thegeneral procedures set forth herein will be apparent to those skilled inthe art.

EXAMPLE 1 A mixture of 12.7 g. of magnesium and 56.7 g. of3-methoxypropyl chloride in 300 ml. of ether is refluxed for 1 hour. Theresulting mixture is cooled to about 10 C. and a suspension of 34.3 g.of 2-chloro-l0-anthrone in 250 m1. of ether is added. The reactionmixture is allowed to warm to room temperature and stand overnight. Mostof the ether is removed and the residue decomposed with ammonium sulfatein a minimum of water plus ice. The mixture is extracted with ether, theextract evaporated and the residue taken up into benzene. The benzene isextracted with alkali and then evaporated to give 2- chlorol O-hydroxyl-3-methoxypropyl )-9, l 0- dihydroanthracene.

A solution of 28.7 g. of the above 9,10-dihydroanthracene in 1 ml. of 48percent hydrobromic acid and 225 ml. of glacial acetic acid is refluxedfor 6 hours. The reaction mixture is then concentrated, diluted withwater and made strongly alkaline. The solution is extracted with etherand the dried extract is chromatographed on alumina to give2-chloro-l0-( 3- bromopropyl)-anthracene, m.p. 77-78 C.

Into a solution of 10.0 g. of the above anthracene in 30 ml. of benzeneis bubbled about 12 g. of dimethylamine at room temperature. Theresulting mixture is heated in a pressure bottle on a steam bath for 4hours, cooled and allowed to stand. The reaction mixture is made basic,treated with ether and filtered. The separated, dried ether solution isevaporated to give 2-ch1orol 0-( 3-dimethylaminopropyl )-anthracene;hydrochloride salt, m.p. 234235 C.

A mixture of 2.0 g. of the above salt free base and 2.0 g. of redphosphorus in 10 ml. of 57 percent hydroiodic acid is refluxed for 24hours The reaction mixture is diluted with water, filtered, made basicand extracted with ether to give 2' chlorol 0-(3-dimethylaminopropyl)-9. l O-dihydroanthracene; hydrochloride salt,m.p. l-203 C EXAMPLE 2 A mixture of 18.2 g. of 2-chloro-l0( 3-bromopropyl)anthracene (prepared asin example 1 and l 1.0 g. ofN-methylpiperazine in 50 ml. of toluene is refluxed for 24 hours. Thereaction mixture is made basic and extracted with ether to give2-chloro-10-[3-(N'-methyl-N-piperazinyl)-- propyll anthrancene;hydrochloride salt, m.p. 260 C. dec.

A mixture of 2.0 g. of the above free base and 2.0 g. of red phosphorusin 10 ml. of 57 percent hydroiodic acid is refluxed for 24 hours. Thereaction mixture is diluted, filtered and made basic to give2-chloro-l0-l 3-(N-methyl-N-piperazinyl)-propyll-9,lO-dihydroanthracene; hydrochloride salt, m.p. 233 C. dec.

Similarly, by employing an equivalent amount of dibutylamine instead ofN-methypiperazine in the above sequence, there is obtained 2-chloro-l0-(3-dibutylaminopropyl)-9.l0- dihydroanthracene.

EXAMPLE 3 To a solution of 20 g. of2-bromo-4-trifluoromethylbenzonitrile in 300 ml. of ether is added 29ml. of a 3M solution of phenylmagnesium bromide in 100 ml. of ether andthe resulting mixture is refluxed for 3 hours, then stirred for 16 hoursat room temperature. The dried ether solution is evaporated and theresidue treated with excess dilute hydrochloride acid to give the iminewhich is heated on the steam bath for l hour. This mixture is extractedwith ether to give after fractional distillation,2-bromo-4-trifluoromethylbenzophenone, m.p. 52-53 C.

A mixture of 12.5 g. of the above benzophenone and 12.5 g. of redphosphorus in 25 ml. of 57 percent hydroiodic acid is refluxed andstirred under nitrogen for 24 hours. The reaction mixture is dilutedwith water, filtered and solid washed with ether and water. The ethersolution is dried and evaporated to give2-bromo-4-trifluoromethyldiphenylmethane, b.p. 97-l00 C./0.'2 mm.

The Grignard reagent prepared from 5.0 g. of the above diphenylmethaneand 0.4 g. of magnesium in 50 ml. of tetrahydrofuran is poured into 200ml. of ether saturated with carbon dioxide at C. The reaction mixture isextracted with dilute sodium hydroxide solution, neutralized with diluteacid and concentrated, The residue is taken up in ether, washed withdilute hydrochloride acid, dried and concentrated to giveZ-benzyl-S-trifluoromethylbenzoic acid, m.p.

A solution of 19.9 g. of the above acid, in 58 ml. of concentratedsulfuric acid is stirred at room temperature for 3 hours, poured into700 ml. of water and filtered to give 2- trifluoromethyl-lOanthrone,m.p. l48-150 C.

A mixture of 8.65 g. of 3-methoxypropyl chloride and 1.9 g. of magnesiumin 100 ml. of ether is stirred and refluxed for 2 hours. To this mixtureat 10 C. is added a suspension of 6.0 g. of 2-trifluromethyl-lO-anthronein ether. After stirring for 3 hours at 10 C., then 16 hours at roomtemperature, the reaction mixture is poured into ammonium chloridesolution and extracted with ether. The extract is evaporated, taken upin benzene, extracted with base, washed with water. dried and evaporatedto give 2-trifluoromethyl-l0-hydroxy-10-( 3- methoxypropyl)-9,lO-dihydroanthracene. The latter 2.0 g., 111 7.5 ml. of 48 percenthydrobromic acid and 14 ml. of glacial acetic acid is refluxed for 6hours. The reaction mixture is evaporated, taken into ether andchromatographed to give 2- trifluoromethyll 04 3-bromopropyll-anthracene, m.p. 87-88 C.

The above anthracene 15.0 g.) and 18 g. of dimethylamine in 45 m1. ofbenzene is heated on the steam bath in a pressure bottle for 6 hours.The reaction mixture is treated with water and extracted with dilutehydrochloric acid. The acid extract is made basic, extracted with etherand the dried ether extract IS evaporated to give Z-trifluoromethyh l0-( 3 dimethylaminopropyl)-anthracene b.p. -160 C./0.35 mm.

A mixture of 3.8 g. of the above anthracene, 0.6 g. of copper chromiteand 15 ml. of Decalin is heated at 200 C. under 4,000 lbs. hydrogenpressure for 3 hours to give upon workup the product2-trifluoromethyl-l0-(3- dimethylaminopropyl)9,10-dihydroanthracene;hydrochloride salt, m.p. l94.5-196 C.

EXAMPLE 4 To a mixture of 0.72 g. of sodium hydride (56 percent)suspension in mineral oil) nd 3.7 g. of trimethylsulfoxonium iodide in25 ml. of dimethylsulfoxide is added 5.0 g. of 2-bromo-4-trifluoromethylbenzophenone (prepared as in example 3) in 8 ml.of dimethysulfoxide. The resulting mixture is stirred for 30 minutes atroom temperature then heated at 5055 C. for 90 minutes. The reactionmixture is poured into water, extracted with ether, and the extractevaporated to give l-phenyl-1-(-bromo-4-trifluoromethylpheny1)-ethyleneoxide, m.p. 77-78 C.

The above oxide 12.7 g.) in 55 ml. of ether is added to 1.0 g. oflithium aluminum hydride in 55 ml. of ether and the mixture is refluxedfor 1 hour. Water (2 ml.) is added and the reaction mixture is filteredto give a-phenyl-a-(2-bromo-4- trifluoromethylphenyl)-ethanol. Thelatter (12.5 g.) is refluxed and stirred with 12.5 g. of red phosphorusand 25 ml. of 57 percent hydroiodic acid for 24 hours. The reactionmixture is filtered to give2-(a-methylbenzyD-S-trifluoromethylbromobenzene.

A mixture of 2.4 g, of the above bromobenzene, 0.7 g. of cuprous cyanideand 1.5 ml. of dimethylformamide is stirred and refluxed for 4 hours.The reaction mixture is poured into a solution of 3.1 g. of ferricchloride in 4.5 ml. of water and 0.8 m1. of concentrated hydrochloricacid, extracted with chloroform, water-washed, dried and distilled togive 2-(amethylbenzyl)-5-trifluoromethylbenzonitrile.

To the Grignard solution formed with 6.2 g. of 3-methoxypropyl chlorideand 1.4 g. of magnesium in 75 ml. of tetrahydrofuran is added 5.0 g. ofthe above nitrile in 50 ml. of tetrahydrofuran and the mixture isrefluxed for 2 hours. The reaction mixture is decomposed with ammoniumchloride solution and extracted with ether. The dried ether extract isevaporated to give the methoxypropyl imine (29 g.) which is refluxed for6 hours in 100 ml. of 48 percent hydrobrornic acid and 200 ml. of aceticacid. The reaction mixture is evaporated, extracted with ether and thedried extract chrmatographed to give 2-trifluoromethyl-9-methyl-10,-( 3-bromopropyl )-anthracene.

' A mixture of 12.0 g. of the above anthracene and 18 g. ofdimethylamine in 60 ml. of dry benzene is heated in a pressure bottle onthe steam bath for hours. The reaction mixture is treated with water andextracted with diluted hydrochloric acid. The acid extract is madebasic, extracted with ether and the dried extract evaporated to give2-trifluoromethyl-9- methyl-l0-(3-dimethylaminopropyl)-anthracene, b.p.165-170C./O.l mm.; hydrochloride salt, m.p. 263 C. (dec.).

The above anthracene (2.0 g.) is reduced with 0.34 g. of copper chromitein 4 ml. of Decalin at 200 C. and 4,000 lbs. of hydrogen for 3 hours togive 2-trifluoromethyl-9-methyl-1O 3-dimethylaminopropy1)-9, 1O-dihydroanthracene; hydrochloride salt, m.p. 179-1 81 C. This is thecis-isomer.

Similarly, reaction of 2-trifluoromethyl-9-methyl-10-( 3-bromopropyl)-anthracene with N-methylpiperazine as described abovefollowed by reduction yields the corresponding2-trifluoromethyl-9-methyll 0-[ 3-(N'-methyl-N-piperazinyl)-propyl]-9,10-dihydroanthracene EXAMPLE 5 Amixture of 12.0 g. of 2trifluoromethyl-l0-(3- bromopropyl)-anthracene(prepared as in example 3) and 4.9 of N-methylpiperazine in 40 ml. ofbenzene is heated in a pressure bottle on the steam bath for 12 hours.Water is added to the reaction mixture, made basic and benzene separatedwhich gives Z-trifluoromethyll O-[3-N-methyl-N-piperazinyl)-propyl]-anthracene, b.p. 185-189 hydrochloridesalt, m.p. 280 C. (dec.).

The above anthracene free base (4.6 g.) in 10 ml. of Decalin and 0.74 g.of copper chromite are heated at 200 C. and 4,000 lbs. hydrogen to give2-trifluoromethyl-lO-[3-(N- methyl-N-piperazinyl )-propyl ]-9, lO-dihydroanthracene; hydrochloride salt, m.p. 263 C.

Similarly, in the above reaction sequence, reacting an equivalent amountof pyrrolidine or piperidine instead of N- methylpiperazine results inthe formation of 2- trifluoromethyll 0[ 3-( N-pyrrolidinyl )-propyl ]-9,l 0- dihydroanthracene and2-trifluoromethyl-l0-(3-(N-piperidinyl)-propyl]-9, IO-dihydroanthracene,respectively.

C./0.1 mm.;

EXAMPLE 6 Following the general procedures of example 1, a mixture of12.7 g. of magnesium and 64.0 g. of 3-methoxy-2-methylpropyl chloride in300 ml. of ether is treated with 31.2 g. of 2- methyl-lO-anthrone in 250m1. of ether to give 2-methyl-10-hydroxy-10-(3-methoxy-2-methylpropyl)-9,10- dihydroanthracene. Thelatter is similarly dehydrated and hydrolyzed with 48 percenthydrobrornic acid and the bromo compound reacted with dimethylamine togive 2'methyl-10-( 3 -dimethylamino-2-methylpropyl)-anthracene.Reduction with red phosphorous and 57 percent hydroiodic acid yields theproduct, 2-methyl- 1 0-( 3-dimethylamino-2methylpropyl )9 ,10-dihydroanthracene.

EXAMPLE 7 Following the procedure outlined in example 3 2-trifluoromethyl-l0-(3-bromopropyl)-anthracene (15.0 g.) is treated withexcess aqueous ammonia, methylamine or butylamine to give afterreduction the products, 2trifluoromethyl- 1 0-( 3-aminopropyl )-9, l 0-dihydroanthracene, 2-trifluor0methyll 0-( 3-methalaminopropyl)9,10-dihydroanthracene and 2-trifluoromethyl-10-(3-butylaminopropyl)-9,l0-

dihydroanthracene, respectively.

EXAMPLE 8 EXAMPLE 9 A mixture of 10 g. of2-trifluoromethyI-9-methyl-10-(3- dimethylaminopropyl)-anthracene(prepared as in example 4), 15 g. of red phosphorus and 70 ml. of 57percent hydroiodic acid solution is refluxed and stirred for 40 minutes.The reaction mixture is poured into water, made basic with sodiumhydroxide solution, stirred for 1 hour with solution ether and filtered.The dried filtrate is evaporated in vacuo to give the free base which isa mixture consisting of about percent of the transand 20 percent of thecisisomer of 2- trifluoromethyl-9-methyl-10-( 3-dimethylaminopropyl)-9,10- dihydroanthracene. Recrystallization of the hydrochloride salt ofthe mixture from a acetone-ethyl acetate yields the pure trans-isomerhydrochloride, m.p. 200-201C.

EXAMPLE 10 A mixture of 18.5 g. of l-di-p-to1uoyltartaric acid and 16.7g. of cis-2-trifluoromethyl-9-methyl-10-(3-dimethylaminopropyl)-9,lo-dihydroanthracene (prepared as in example 4 on100 ml. of boiling methanol and 10 ml. of water yields thel-di-p-toluoyltartrate salt, m.p. 167 C. (foam), [a],, =+3.66. The freebase liberated from this salt with ammonium hydroxide and ether isconverted to the hydrochloride salt ofd-cis-2-trifluoromethyl-9-methyl-10-( 3- dimethylaminopropy1)-9,IO-dihydroanthracene, m.p. 209-210C., [a],, =+9.62 (2 percent ethanol).

The filtrate from the crude l-di-p-toluoyltartrate salt above is treatedwith ammonium hydroxide and ether to regenerate 13.5 g. of the cis freebase. The latter with 15.0 g. of d-di-ptoluoyltartaric acid in 200 ml.of methanol and 20 ml. of water forms the d-di-p-toluoyltartrate salt,[a],, =-2.4 (1 percent ethanol). The liberated free base is converted tothe hydrochloride salt of l-cis-2-trifluoromethyl-9-methyl-10-( 3-dimethylaminopropyl )-9, 1 O-dihydroanthracene, mp. 206208C., [a],,"=9.6 (2 percent ethanol).

EXAMPLE 1 1 To a solution of 71.8 g. of2-benzy1-S-trifluoromethylbenzonitrile (prepared from2-bromo-4-trifluoromethyldiphenylmethane by reaction with cuprouscyanide) in 100 ml. of ether is added gradually 183 ml. of 3M methylmagnesium bromide in ether. The reaction mixture is refluxed withstirring for 6 hours, decomposed with aqueous ammonium chloride,extracted with ether and evaporated. The residue is taken up in 250 ml.each of 48 percent hydrobromic acid solution and acetic acid, refluxedfor 18 hours, evaporated and extracted with chloroform. The filteredextract is evaporated, the residue is dissolved in methanol and thesolvent removed to give 2-trifluoromethyl-10-methylanthracene, m.p.98100 C. 1

A mixture of the above prepared anthracene (33.2 g.) and 34.2 g. ofN-bromosuccinimide in 300 ml. of carbon tetrachloride, catalyzed by 0.34g. of benzoyl peroxide, is refluxed and stirred for 2 hours. The hotreaction mixture is filtered and cooled to precipitate2-trifluoromethyl-10- bromomethylanthracene.

To 5.2 g. of 57 percent sodium hydride in 100 ml. of dimethysulfoxide at50 C. is added slowly a solution of 19.8 g. of diethylmalonate indimethylsulfoxide and the mixture is heated at 75 C. for 45 minutes. Aslurry of 36.5 g. of 2- trifluoromethyl-lO-bromoethylanthracene indimethylsulfoxide is added and the resulting mixture is heated at 75 C.for 1 hour. The reaction mixture is quenched with water and extractedwith ether to give diethyl (3-trifluoromethyl-10-anthracenyl)-methylmalonate. The latter (50.7 g.) is hydrolyzed with 41g. of potassium hydroxide in 200 ml. of 60 percent ethanol to the freemalonic acid which is heated at 185200C. to obtain2'-trifluoromethylanthracene-10- propionic acid.

A mixture of 32.7 g. of the above prepared propionic acid and 48 g. ofred phosphorus in 160 ml. of 57 percent hydroiodic acid and 75 ml. ofacetic acid is refluxed and stirred for 3 hours. The reaction mixture isdiluted with water, extracted with chlorofonn, washed with water andevaporated to yield 2-trifluoromethyl-9, 1 O-dihydroanthracene- 1propionic acid, m.p. 153-155 C.

A solution of 8.0 g. of 2-trifluoromethyl-9,l0-dihydroanthracene-lO-propionic acid and 3.0 g. of d-aphenethylamine in45 ml. of ethanol is clouded with 50 ml. of water while boiling to givethe d-a-phenethylamine salt, m.p. 179-18lC., [a],,"' 3.2 (1 percentethanol). This salt is acidified with hydrochloric acid, extracted withether and the dried extract evaporated to give l-2-trifluoromethyl-9,l0-dihydroanthracene-IO-propionic acid. The latter is refluxed with ml. ofthionyl chloride for 2 hours and the resulting acid chloride dissolvedin 20 ml. of benzene is saturated with dimethylamine to yield thedimethylamide. The amide (2.2 g.)

in ether is added to 1.1 g. of lithium aluminum hydride in ether,refluxed for 1 hour and worked up to give d-2- trifluoromethyll 0-(3-dimethylaminopropyl )-9, l 0- dihydroanthracene; hydrochloride salt,mp. 201-202 C., [a] =+4.92 1 percent ethanol).

The filtrate from the crude d-a-phenethylamine salt above is evaporated,acidified and extracted with ether to regenerate2-trifluoromethyl-9,IO-dihydroanthracene-10-propionic acid. The latter(6.2 g.) and 2.4 g. of l-a-phenethylamine dissolved in 30 ml. of ethanolis clouded while boiling with 50 ml. of water to give thel-a-phenethylamine salt, m.p. 177-l79 C., [a],, =+3.46. This salt isacidified to liberate d-2- trifluoromethyl-9, 1 O-dihydroanthracenelO-propionic acid which is treated as above with thionyl chloride, theacid chloride reacted with dimethylamine and the amide reduced withlithium aluminum hydride to yield l-2-trifluoromethyl- 1 0-(3-dimethylaminopropyl )-9, 1 O-dihydroanthracene; hydrochloride salt,m.p. 200-202 C., [a],,**=5.73 (l percent ethanol).

EXAMPLE 12 Following the general procedure of example 3, 18.2 g. of 2-bromo-4-methylthiobenzonitrile (obtained from 4- methylthiobenzonitrile)and 29 ml. of 3M phenylmagnesium bromide in ether solution are reactedto give 2-bromo-4- methylthiobenzophenone. A mixture of the latter andred phosphorus in 57 percent hydroiodic acid is refluxed and stirredunder nitrogen for 24 hours to 2-bromo-4- methylthiodiphenylmethane. TheGrignard reagent prepared from this diphenylmethane in tetrahydrofuranis poured into ether saturated with carbon dioxide at C. Workup yields2-benzy1-5-methylthiobenzoic acid. A solution of the acid inconcentrated sulfuric acid is stirred. at room temperature to give thering-closed product, 2-methylthio-10-anthrone.

To the Grignard reagent prepared from 8.65 g. of 3-methoxypropylchloride in ether is added a suspension of 5.5 g. of2methylthio-l0-anthrone in ether. After stirring for 3 hours at 10 C.and 18 hours at room temperature, the reaction mixture is decomposed andworked up to give 2-methylthio-l0-hydroxy-10(3-methoxypropyl)-9,l0dihydroanthracene. The latter isrefluxed in 48 percent hydrobromic acid and glacial acetic acid to give2-methylthio-10-( 3-bromopropyl)- anthracene.

The above anthracene 13.7 g.) and 18 g. of dimethylamine in benzene isheated on the steam bath in a pressure bottle for 6 hours to give uponworkup 2-methylthio-10-( 3- dimethylaminopropyl)-anthracene which ishydrogenated in the presence of copper chromite to yield2-methylthio-10-(3- dimethylaminopropyl)-9,10-dihydroanthracene.

Similarly, by employing 2-bromo-4-methylsulfonylbenzonitrile (obtainedfrom the 4-methylthio derivative by oxidation with chromic anhydride insulfuric acid) in the above described reaction sequence there isobtained as a final product, 2-methylsulfonyl-10-(3-dimethylaminopropyl)-9, l0- dihydroanthracene.

EXAMPLE 1 3 Following the general procedure of example 3, 16.8 g. of 3-bromo-4-cyano-N,N-dimethylbenzenesulfonamide (obtained from4-cyano-N,N-dimethylbenzenesulfonamide in ether is reacted with 29 m1.of 3M phenylmagnesium bromide in ether and the mixture worked up to give2-bromo-4N,N-dimethylsulfamy)-benzophenone which is reduced with redphosphorus and hydroiodic acid to the corresponding diphenylmethane. TheGrignard reagent prepared from this diphenylmethane is reacted withcarbon dioxide with cooling to give2-benzyl-5-(N,N-dimethylsulfamyl)-benzoic acid. Ring closure is effectedvia concentrated sulfuric acid to yield 2-( N,N dimethylsulfamyll0-anthrone The Grignard reagent prepared from 8.65 g. of3-methoxypropyl chloride is reacted with 5.0 g. of the above-preparedanthrone to give 2-( N,N-dimethylsulfamyl)-10-hydroxy-10- hours(3-methoxypropyl)-9,lO-dihydroanthracene. The latter is refluxed in 48percent hydrobromic acid and glacial acetic acid to give2-(N,N-dimethylsulfamyl)-l0-(3-bromopropyl)- anthracene.

The above anthracene 12.6 g.) and 18 g. of dimethylamine in benzene isheated on the steam bath in a pressure bottle for 6 hours to give uponworkup 2-(N,N-dimethylsulfamyl)-10-(3 -dimethylaminopropyl)-anthracenewhich is hydrogenated in the presence of copper chromite to yield2-(N.N-dimethysu1famyl)-l0-(3-dimethylaminopropyl)-9,10-dihydroanthracene.

EXAMPLE 14 To a solution of 32.9 g. of2-br0mo-4-trifluoromethylbenzophenone in 400 ml. of ether is added oneequivalent of ethylmagnesium bromide in ether and the resulting mixtureis refluxed for 4 hours. Treatment with aqueous acid gives aphenyl-a-(2-bromo-4-trifluoromethylphenyl )-propanol. The latter (13.0 g.) isrefluxed and stirred with 12.5 g. of red phosphorus and 25 ml. of 57percent hydroiodic acid for 24 to yield 2-( a-ethylbenzyl )-5-trifluoromethylbromobenzene.

A mixture of 2.5 g. of the above bromobenzene, 0.7 g. of cuprous cyanideand 1.5 ml. of dimethylformamide is stirred and refluxed for 4 hours.The reaction mixture is poured into a solution of 3.1 g. of fericchloride in 4.5 ml. of water and 0.8 ml. of concentrated hydrochloricacid, extracted with chloroform, water-washed, dried and distilled togive 2-(aethylbenzyl)S-trifluoromethylbenzonitrile.

To the Grignard reagent formed with 6.2 g. of 3-methoxypropyl chloridein 75 ml. of tetrahydrofuran is added 5.2 g. of the above nitrile andthe mixture is refluxed for 2 hours. The decomposed reaction mixtureyields the methoxypropyl imine which is refluxed for 6 hours in 100 ml.of 48 percent hydrobromic acid and 200 ml. of acetic acid. The reactionmixture is evaporated, extracted with ether and the dried extractchromatographed to give 2-trifluoromethyl-9-ethyl-l0-(3-bromopropyl)-anthracene.

A mixture of 12.5 g. of the above anthracene and 18 g. of dimethylaminein 60 ml. of dry benzene is heated in a pressure bottle on a steam bathfor 5 hours. The reaction mixture is heated with water and extractedwith dilute hydrochloric acid. The acid extract is made basic andfurther worked up to give2-trifluoromethyl-9-ethyl-10-(3-dimethylaminopropyl)- anthracene. Thelatter (2.8 g.) is reduced with 0.34 g. of copper chromite in 4 ml. ofDecalin at 200 C. and 4,000 lbs. of hydrogen to yieldZ-trifluoromethyl-Q-ethyl-10-(3- dimethylaminopropyl )-9, lO-dihydroanthracene.

Similarly by commencing the above sequence of reaction employingphenylmagnesium bromide instead of ethylmagnesium bromide there isobtained the corresponding 2- trifluoromethyl-9-phenyll 0-(3-dimethylaminopropyl )-9, 1 0- dihydroanthracene.

EXAMPLE To a suspension of 2.1 g. of 57 percent sodium hydride in 45 ml.of dimethylsulfoxide in added gradually, with stirring, 7.5 g. of9-methyl-9,IO-dihydroanthracene and the mixture heated at 70 C. for 2hours. A solution of 7.5 g. of 3- dimethylaminopropyl chloride in 30 ml.of dimethylsulfoxide is added and heating is continued for 3 hours. Thereaction mixture is quenched with water, extracted with ether and theether extracted with dilute hydrochloric acid. The acid extract is madebasic to give the liberated base. 9-methyl-l0-(3- dimethylaminopropyl )91 Odihydroanthracene, hydrochloride salt, m.p 213-216 C EXAMPLE 16 To asolution of 24.8 g. of 9-methyI-9,l0- dihydroanthracene in 300 ml ofether is added over 15 minutes 96 ml. of 15 percent lithium in hexaneand the resulting mixture is stirred at room temperature for 2 hours.After adding 24.6 g. of B-dimethylaminopropyl chloride, the mixture isstirred and refluxed for 3 hours and allowed to stand overnight Thereaction mixture is extracted with dilute hydrochloric acid, made basic,extracted with ether and distilled to give the free base, b.p. 160C./0.5 mm. The latter is fractionated and the first fraction collectedat b.p. -139" C./0.15 mm. is cis-9-methyl-10-(3-dimethylaminopropyl)-9,10-dihydroanthracene; hydrochloride salt, m.p. 2 17-2 1 8 C The secondfraction obtained from above (4.5 g.) is heated about 1 hour at 70 C.with 0.81 g. of 57 percent sodium hydride in 40 ml. ofdimethylsulfoxide. The reaction mixture is quenched in water, extractedwith ether, dried and evaporated. The residual free base is converted toa hexamate salt in acetone and recrystallized from acetonitrile to givetrans-9-methyl-l0-(3-dimethylaminopropyl)-9,10- dihydroanthracenehexamate, m.p. 169-17 1 C.

What we claim is:

1. A chemical compound of the structural formula:

in which:

R is hydrogen, lower alkyl or phenyl;

Y is halogen having an atomic weight of less than 80, lower alkyl,trifluoromethyl, lower alkylthio or lower alkylsulfonyl;

A is an alkylene chain of two to four carbon atoms; and

Z is amino, mono-loweralkylamino or di-loweralkyl-amino,

each of said lower alkyl or alkoxy moieties having from one to fourcarbon atoms, or its nontoxic, pharmaceutically acceptable, acidaddition salt.

2. A chemical compound in accordance with claim 1 in which R ishydrogen, methyl, ethyl, or phenyl; Y is the 2-position; A is propyleneand Z is dimethylamino.

3. A chemical compound in accordance with claim 2 in which Y ischlorine, methyl, trifluoromethyl, methylthio or methysulfonyl.

4. A chemical compound in accordancewith claim 1 in which R is hydrogenor methyl; Y is trifluoromethyl and Z is monomethylamino ordimethylamino.

5. A chemical compound in accordance with claim 4 in which Y is2-trifluoromethyl.

6. A chemical compound in accordance with claim 5 in which A ispropylene.

7. A chemical compound in accordance with claim 6 in which Z isdimethylamino.

8. A chemical compound in accordance with claim 7 in which R ishydrogen, being the compound 10-(3- dimethylaminopropyl)-2-trifluoromethyl-9, l O- dihydroanthracene.

9. The d-isomer of the compound in accordance with claim 8.

10. The l-isomer of the compound in accordance with claim 8.

11 A chemical compound in accordance with claim 7 in which R is methyl,being the compound 9-methyl-10-( 3-dimethylaminopropyl)-2-trifluoromethyl-9, 10- dihydroanthracene.

12. The cis-isomer of the compound in accordance with claim ll 13. Thed-isomer of the compound in accordance with claim l2.

14 The l-isomer of the compound in accordance with claim 12.

15 The trans-isomer of the compound in accordance with claim 11 16. Achemical compound of the structural formula:

in which:

R is lower alkyl or phenyl;

A is an alkylene chain of two to four carbon atoms; and

Z is amino, mono-loweralkylamino or di-loweralkylamino;

each of said lower alkyl of alkoxy moieties having from one to fourcarbon atoms, or its nontoxic, pharmaceutically acceptable, acidaddition salt.

21. A chemical compound in accordance with claim 20 in which R, is loweralkyl, A is propylene and Z is dimethylamino.

22. A chemical compound in accordance with claim 21 in which R, ismethyl, being the compound 9-methyl-lO-( 3- dimethylaminopropyl )-9, 1O-dihydroanthracene.

23. The cis-isomer of the compound in accordance with claim 22.

24. The trans-isomer of the compound in accordance with claim 22.

mg UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,622 Dated November 23 1971 Inventor) Paul N. Craig and Charles L.Zirlcle.

It is certified that error appears in the above-identified patent andthat said Letters Patent are hereby corrected as shown below:

Column 3, lines 35-45, reaction sequence indicated as: CH CH l 3 i 3 Y lU CH O-A-MgX Y I CN k -.1 should read: 3

V A Y Column 4, lines 37-46, under the structural formulas should appear(from left to right) CIS TRANS Column 5, lines 35-45, the structuralformula under D;

*zggg UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Pa 3,622,630 Dated November 23 1971 Inventor) Paul N. Craig and Charles L.Zirkle It is certified that error appears in the above-identified patentand that said Letters Patent are hereby corrected as shown below:

Column 5, line +1, delete the second occurrence of:

Signed and sealed this 20th day of June 1972.

(SEAL) fittest:

JDNARD ILFLETCHEH, JR. ROBERT GOTTSCHALK Attesting Officer Commissionerof Patents

2. A chemical compound in accordance with claim 1 in which R ishydrogen, methyl, ethyl, or phenyl; Y is the 2-position; A is propyleneand Z is dimethylamino.
 3. A chemical compound in accordance with claim2 in which Y is chlorine, methyl, trifluoromethyl, methylthio ormethysulfonyl.
 4. A chemical compound in accordance with claim 1 inwhich R is hydrogen or methyl; Y is trifluoromethyl and Z ismonomethylamino or dimethylamino.
 5. A chemical compound in accordancewith claim 4 in which Y is 2-trifluoromethyl.
 6. A chemical compound inaccordance with claim 5 in which A is propylene.
 7. A chemical compoundin accordance with claim 6 in which Z is dimethylamino.
 8. A chemicalcompound in accordance with claim 7 in which R is hydrogen, being thecompound10-(3-dimethylaminopropyl)-2-trifluoromethyl-9,10-dihydroanthracene. 9.The d-isomer of the compound in accordance with claim
 8. 10. Thel-isomer of the compound in accordance with claim
 8. 11. A chemicalcompound in accordance with claim 7 in which R is methyl, being thecompound 9-methyl-10-(3-dimethylaminopropyl)-2-trifluoromethyl-9,10-dihydroanthracene.
 12. The cis-isomer of the compound in accordancewith claim
 11. 13. The d-isomer of the compound in accordance with claim12.
 14. The l-isomer of the compound in accordance with claim
 12. 15.The trans-isomer of the compound in accordance with claim
 11. 16. Achemical compound of the structural formula:
 17. A chemical compound inaccordance with claim 16 in which R is hydrogen and Y is2-trifluoromethyl.
 18. A chemical compound in accordance with claim 17in which A is propylene.
 19. A chemical compound in accordance withclaim 18 in which Z is dimethylamino.
 20. A chemical compound of thestructural formula:
 21. A chemical compound in accordance with claim 20in which R2 is lower alkyl, A is propylene and Z is dimethylamino.
 22. Achemical compound in accordance with claim 21 in which R2 is methyl,being the compound9-methyl-10-(3-dimethylaminopropyl)-9,10-dihydroanthracene.
 23. Thecis-isomer of the compound in accordance with claim
 22. 24. Thetrans-isomer of the compound in accordance with claim 22.